While it is widely recognized that a host of common diseases and disease outcomes differ among populations defined by continental ancestry, it is usually unclear what the relative contributions of different patterns of environmental exposures, different access to and utilization of health care resources, and the different frequencies of alleles affecting risk of disease or outcomes are to the observed differences in risk of disease and outcomes. We focus in this project largely on building tools to identify and characterize, with respect to function and biological mechanism, the genetic risk factors contributing to health disparities in disease and outcomes, and then in the application of these tools to disease and outcome phenotypes relevant to our project and to the larger health disparities research community. Our applications will be made in the context of Vanderbilt University's research database of electronic health records (EHR), the Synthetic Derivative, with data on more than 2.5 million subjects going back almost 30 years, and linked biobank (BioVU), with DNA samples on more than 200,000 subjects. This will allow us to leverage large and ongoing investments made by Vanderbilt to build and enhance these resources. For example, we will be able to access genome data on more than 100,000 BioVU subjects, including more than 17,000 African Americans for our project to identify and characterize the genetic component to health disparities in African Americans. All software tools we develop for this research will be made publicly available, and we will in addition construct publicly accessible databases ? the Vanderbilt Health Disparities Portal ? serving the results of our studies. Thus, in addition to the discovery research we will conduct, we seek to provide resources that will enhance research infrastructure in health disparities for the entire scientific community. Our Specific Aims are to: 1) Systematically identify phenotypes with marked differences in lifetime risks between Americans of recent European and Americans of recent African ancestry. These studies will be conducted using the SD with EHR on more than 2.5 million patients within VUMC. 2) Systematically identify and characterize the genetic factors contributing to phenotypes with significantly different lifetime risks among individuals from populations with different historical geographic ancestry. These studies will be conducted using BioVU, in which we have DNA samples on more than 200,000 subjects, with genome interrogation (ranging from whole genome sequencing to genome-wide association studies using genotyping arrays) available on more than 100,000 subjects, including more than 17,000 African Americans, by the end of 2016. 3) Comprehensively characterize the relative contribution of genetic risk factors to health disparities in lifetime risk and outcomes for a) asthma and pre-term birth (year 1), phenotypes with existing support for genetic contributions to health disparities, b) cervical cancer and BMI (year 2), phenotypes investigated in our other projects, and c) phenotypes discovered through research conducted in Aims 1 and 2, chosen from other grants funded in this initiative, or are disparities in the LGBT community (years 3-5).